Journal
WOUND REPAIR AND REGENERATION
Volume 23, Issue 5, Pages 644-656Publisher
WILEY-BLACKWELL
DOI: 10.1111/wrr.12337
Keywords
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Funding
- NCI NIH HHS [P30 CA016059] Funding Source: Medline
- NCRR NIH HHS [S10RR031535, C06 RR017393] Funding Source: Medline
- NHLBI NIH HHS [R01 HL125353, R01 HL072925, HL072925] Funding Source: Medline
- NIAID NIH HHS [R21 AI109068] Funding Source: Medline
- NICHD NIH HHS [U01 HD087198] Funding Source: Medline
- NIH HHS [NH1C06-RR17393, S10 OD010641] Funding Source: Medline
- BLRD VA [I01 BX001792] Funding Source: Medline
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Very little is known about lipid function during wound healing, and much less during impaired healing. Such understanding will help identify what roles lipid signaling plays in the development of impaired/chronic wounds. We took a lipidomics approach to study the alterations in lipid profile in the LIGHT(-/-) mouse model of impaired healing which has characteristics that resemble those of impaired/chronic wounds in humans, including high levels of oxidative stress, excess inflammation, increased extracellular matrix degradation and blood vessels with fibrin cuffs. The latter suggests excess coagulation and potentially increased platelet aggregation. We show here that in these impaired wounds there is an imbalance in the arachidonic acid (AA) derived eicosonoids that mediate or modulate inflammatory reactions and platelet aggregation. In the LIGHT(-/-) impaired wounds there is a significant increase in enzymatically derived breakdown products of AA. We found that early after injury there was a significant increase in the eicosanoids 11-, 12-, and 15-hydroxyeicosa-tetranoic acid, and the proinflammatory leukotrienes (LTD4 and LTE) and prostaglandins (PGE(2) and PGF(2)). Some of these eicosanoids also promote platelet aggregation. This led us to examine the levels of other eicosanoids known to be involved in the latter process. We found that thromboxane (TXA(2)/B-2), and prostacyclins 6kPGF1 are elevated shortly after wounding and in some cases during healing. To determine whether they have an impact in platelet aggregation and hemostasis, we tested LIGHT(-/-) mouse wounds for these two parameters and found that, indeed, platelet aggregation and hemostasis are enhanced in these mice when compared with the control C57BL/6 mice. Understanding lipid signaling in impaired wounds can potentially lead to development of new therapeutics or in using existing nonsteroidal anti-inflammatory agents to help correct the course of healing.
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